中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (32): 5903-5907.doi: 10.3969/j.issn.1673-8225.2010.32.003

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

骨髓间充质干细胞修复损伤肾小管上皮细胞：可能与可行？

万建新，郭  琦，潘阳彬，崔  炯，傅槟槟，许艳芳   

  1. 福建医科大学附属第一医院肾内科，福建省福州市   350005
  • 出版日期:2010-08-06 发布日期:2010-08-06
  • 作者简介:万建新☆，男，1967年生，福建省霞浦县人，汉族，1988年福建医科大学毕业，博士，教授，主任医师，主要从事损伤肾脏的修复与再生的研究。 wanjx@263.net
  • 基金资助:

    福建省自然科学基金资助项目(C0710009)，课题的名称“骨髓间充质干细胞在小鼠急性肾衰竭修复中的作用”

Bone marrow mesenchymal stem cells in repairing damaged renal tubular epithelial cells: Possibility and feasibility?

Wan Jian-xin, Guo Qi, Pan Yang-bin, Cui Jiong, Fu Bin-bin, Xu Yan-fang   

  1. Department of Nephrology, First Affiliated Hospital, Fujian Medical University, Fuzhou  350005, Fujian Province, China
  • Online:2010-08-06 Published:2010-08-06
  • About author:Wan Jian-xin☆, Doctor, Professor, Chief physician, Department of Nephrology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China wanjx@263.net
  • Supported by:

    the Natural Science Foundation of Fujian Province, No. C0710009*

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摘要：

背景：研究表明骨髓间充质干细胞在急性肾损伤后能够通过直接分化为肾小管上皮细胞而促进肾功能的恢复，其修复肾脏的作用机制尚不清楚，能否直接分化为肾小管上皮细胞，目前仍有争议。
目的：观察骨髓间充质干细胞输注后急性肾衰竭小鼠肾功能改变，外源性骨髓间充质干细胞在肾组织的分布以及是否向肾小管上皮细胞分化。
方法：骨髓间充质干细胞来源于绿色荧光蛋白转基因小鼠。8~10周龄的健康雌性昆白小鼠90只随机随机分为3组。急性肾衰竭组和骨髓间充质干细胞组注射顺铂建立急性肾衰竭模型，骨髓间充质干细胞组在建模后24 h经尾静脉输注绿色荧光蛋白转基因小鼠的骨髓间充质干细胞悬液。正常对照组不进行任何干预。建模后第1，4，7，14，28天测定血尿素氮和血肌酐，观察肾组织病理变化，荧光显微镜下观察绿色荧光蛋白阳性的骨髓间充质干细胞在肾组织的分布，共聚焦显微镜下观察骨髓间充质干细胞向肾小管上皮细胞的分化情况。
结果与结论：骨髓间充质干细胞组顺铂注射4~14 d后，尿素氮、肌酐值比急性肾衰竭组明显降低(P < 0.01或P < 0.05)。骨髓间充质干细胞组第4天肾组织中可见绿色荧光的绿色荧光蛋白细胞，分布在外髓质区肾小管，第7天仍可见少量荧光细胞，同时表达肾小管上皮特异性的功能蛋白megalin。结果提示骨髓间充质干细胞在损伤肾脏可直接分化为肾小管上皮细胞，并改善急性肾衰竭小鼠的肾功能。

关键词: 急性肾功能衰竭, 骨髓间充质干细胞, 肾小管上皮细胞, 小鼠

Abstract:

BACKGROUND: Previous studies have suggested that bone marrow mesenchymal stem cells (BMSCs) can directly differentiate into tubular epithelial cells following acute renal failure (ARF) and promote the recovery of renal function. However, the action mechanism of repairing the kidney remains unclear. Whether BMSCs can directly differentiate into tubular epithelial cells is still controversial.
OBJECTIVE: To observe the change in renal function in ARF mice after BMSC infusion and to investigate the distribution of exogenous BMSCs in the kidney and the possibility of BMSC differentiation into tubular epithelial cells.
METHODS: BMSCs were harvested from green fluorescent protein transgenic mice. A total of 90 healthy female Kunming mice aged 8-10 weeks were randomly assigned to three groups. Mice in the ARF group and BMSC group were injected with cisplatin to establish models of ARF. At 24 hours following cisplatin injection, mice in the BMSC group were injected intravenously with BMSCs of green fluorescent protein transgenic mouse. Normal controls were left intact. At 1, 4, 7, 14 and 28 days after cisplatin injection, the blood urea nitrogen and serum creatinine were measured, and renal morphologic changes were observed, distribution of green fluorescent protein-positive BMSCs in the kidney was examined by fluorescence microscopy. Differentiation of BMSCs into renal tubular epithelial cells was observed using confocal microscopy.
RESULTS AND CONCLUSION: After 4-14 days of cisplatin injection, the blood urea nitrogen and serum creatinine value of BMSC group were significantly lower than in ARF group (P < 0.01 or P < 0.05). After 4 days, green fluorescent protein-positive BMSCs were detected in the priopticon area of renal tubule in the BMSC group. On day 7, several green fluorescent protein-positive cells were still detected. Green fluorescent protein-positive BMSCs could express tubular epithelium specific protein megalin. Results have indicated that BMSCs can differentiate into the tubular epithelial cells directly and improve the function of ARF mice.

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